Depression that hasn’t responded to several medications can feel like a closed door. When two or three antidepressants in a row don’t help, it’s natural to wonder what’s left. One direction researchers are exploring is combining two treatments that work in different ways: ketamine and transcranial magnetic stimulation (TMS). Used together, they may support recovery more than either does alone.
At Nushama, we approach this carefully. The evidence is promising but still early, and our protocol differs from the studies you’ll read about. Here’s what the science actually shows, how our accelerated approach with the Ampa One device fits in, and what to consider before pursuing either path.
How ketamine and TMS each work
These two treatments reach the brain by very different routes, which is part of why pairing them is interesting.
IV ketamine (intravenous ketamine, delivered through a vein under medical supervision) acts on the brain’s chemistry. It blocks NMDA (N-methyl-D-aspartate) receptors, which triggers a surge of glutamate, the brain’s main excitatory messenger. That surge sets off a cascade that releases brain-derived neurotrophic factor (BDNF), a protein that supports neuroplasticity — the brain’s ability to form new connections and reorganize old ones. You can read more about how IV ketamine works in the brain in our deeper guide.
TMS (transcranial magnetic stimulation) takes a physical route. It uses focused magnetic pulses to stimulate a specific region — usually the dorsolateral prefrontal cortex, an area that tends to be underactive in depression. There’s no medication and no altered state. You stay awake and alert while a coil rests near your scalp. Our overview of TMS therapy for depression walks through the experience in detail.
So one treatment works through chemistry and one through targeted stimulation. What’s striking is where they meet.
Where the two paths converge
Despite their different starting points, ketamine and TMS arrive at a similar destination inside the neuron. Both increase glutamate signaling, both activate AMPA receptors, and both raise BDNF — the same molecular chain that drives neuroplasticity. A 2023 review in Frontiers in Neuroscience described the two as acting “in a complementary manner,” noting that combining them “may potentiate the effect of either method alone through mutual reinforcement” (Frontiers in Neuroscience, 2023).
This shared pathway is why the device we use is named the Ampa One. AMPA receptors are the brain’s fast-signaling switches, controlling how quickly and strongly neurons talk to each other. TMS activates these receptors at targeted synapses; NMDA receptors then help lock those changes in place through a process called long-term potentiation. Ketamine influences the same receptor system from the chemical side. In other words, the two treatments aren’t just compatible by accident — they’re working on the same biology.
There’s also a timing idea behind combining them. Ketamine appears to open a window of heightened neuroplasticity that lasts a few days. Some clinicians reason that delivering targeted stimulation during that window may help the brain make the most of it, though the precise sequencing is still being studied.
What the research shows so far
The early evidence is encouraging, with the honest caveat that it’s still early.
A 2024 systematic review of combined TMS and ketamine for treatment-resistant depression found that the combination produced “substantial and sustained improvement in depressive symptoms,” with higher efficacy than either treatment used alone. The reviewers also noted that adverse effects were “generally mild and transient,” with no severe events reported in most studies (Cureus, 2024).
The same review is candid about the limits: most of the supporting data comes from case reports and small retrospective studies, with varied designs. Larger randomized trials are needed before anyone can call this a standard protocol. We share that view. Combining ketamine and TMS is a promising direction, not a settled one.
It’s worth separating this from the strong standalone evidence each treatment already has. Accelerated TMS protocols, for example, have shown real results on their own. In a Stanford study of an intensive, individualized form of TMS known as SAINT, “almost 80%” of participants with severe depression reached remission, typically within days, with side effects limited to temporary fatigue and headaches (Stanford Medicine, 2021).
How Nushama’s approach is different
Here’s an important distinction. Most published research on combining TMS with ketamine uses standard, once-daily repetitive TMS (rTMS) spread across six weeks. That is not what we do.
Nushama uses the Ampa One device to deliver accelerated TMS with a technique called intermittent theta-burst stimulation (iTBS). Instead of 36 visits over two months, we can deliver a clinically complete course in compressed form — including Nushama ONE, which fits a full course of short iTBS sessions into a single carefully guided day. You remain awake and yourself throughout; there’s no dissociation, no sedation, and no recovery period. Our guide to accelerated TMS for treatment-resistant depression explains the schedule in more depth.
We also pair iTBS with D-Cycloserine, a medication that modulates NMDA receptors and may enhance the plasticity effects of stimulation. That’s the same receptor family ketamine acts on — another reflection of the AMPA-NMDA science behind the device’s name.
Because our protocol is accelerated rather than the six-week schedule used in most combination studies, we’re thoughtful about how we describe outcomes. The mechanistic logic for pairing accelerated TMS with ketamine is sound, and each treatment has its own evidence base. But the specific combination, in our accelerated form, hasn’t been studied head-to-head. We’d rather tell you that plainly than overstate it.
On ketamine: why IV, and why supervision matters
When ketamine is part of a plan, we use IV infusions rather than at-home lozenges or sprays. Intravenous delivery lets clinicians titrate the dose precisely and monitor you in real time, which supports both safety and consistency. Other routes exist, including Spravato (esketamine, an FDA-approved nasal spray), and we offer that as well. If you’re weighing the options, our comparison of ketamine and other depression treatments may help.
Whatever the route, ketamine works best inside a structure. Medicine can open a window; preparation and integration — the work of making sense of an experience and carrying it into daily life — are how change tends to last. We treat that supportive work as part of the treatment, not an add-on.
Who this may and may not suit
Combining or sequencing these treatments isn’t right for everyone, and eligibility is determined through clinical assessment rather than self-selection.
TMS may not be appropriate if you have a history of seizures, metal implants in or near the head (such as a pacemaker or cochlear implant), or active suicidal thoughts that need inpatient-level care. Ketamine requires its own screening, including review of uncontrolled high blood pressure, certain heart or breathing conditions, active psychosis, and pregnancy. None of this is meant to discourage you — it’s how we make sure a plan fits your body and history.
This article is educational and isn’t medical advice or a diagnosis. The right next step is a conversation with a clinician who can review your full history.
Frequently asked questions
Can you have ketamine and TMS at the same time? Some clinicians use them in parallel but non-simultaneous ways — for example, a course of TMS alongside or shortly after ketamine sessions. The most appropriate sequence depends on your history and goals, which is why a personalized assessment comes first.
Is combining TMS and ketamine FDA-approved? The individual treatments have regulatory standing — TMS devices are FDA-cleared for depression, and Spravato (esketamine) is FDA-approved. The combination as a single protocol is still being researched and isn’t a formally approved regimen. We’re transparent about that.
How is Nushama’s accelerated TMS different from the TMS in research studies? Most combination studies use standard once-daily rTMS over about six weeks. We use the Ampa One device to deliver accelerated iTBS in compressed form, sometimes in a single day. The underlying technology is FDA-cleared; the accelerated schedule is what shortens the timeline.
Will TMS make me feel altered, like ketamine can? No. TMS produces no dissociation and no altered state. You feel a gentle tapping on your scalp and stay fully alert. Ketamine, by contrast, does produce a temporary shift in consciousness, which is one reason we deliver it under close medical supervision.
Does combining treatments mean more side effects? In the studies reviewed so far, combined treatment’s side effects were generally mild and transient. Your care team monitors for them throughout and adjusts as needed.
Taking the next step
Treatment-resistant depression has more options today than it did a decade ago, and the science connecting ketamine and TMS — through glutamate, AMPA receptors, and neuroplasticity — is part of why. The evidence for combining them is promising and still developing, and our accelerated approach with the Ampa One device is its own path rather than a copy of the research protocols.
If you’re curious whether ketamine, accelerated TMS, or a thoughtful combination might fit your situation, the clearest next step is a conversation. Speak with our care team to talk through your history and what a personalized plan could look like.
